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MBE Advance Access originally published online on April 20, 2009
Molecular Biology and Evolution 2009 26(8):1715-1721; doi:10.1093/molbev/msp080
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© The Author 2009. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

Accurate Estimation of Gene Evolutionary Rates Using XRATE, with an Application to Transmembrane Proteins

Andreas Heger*, Chris P. Ponting* and Ian Holmes{dagger}

* Department of Physiology, Anatomy and Genetics, MRC Functional Genomics Unit, University of Oxford, Oxford, United Kingdom
{dagger} Department of Bioengineering, University of California

E-mail: andreas.heger{at}dpag.ox.ac.uk.

Accepted for publication April 11, 2009.

XRATE implements algorithms for comparative annotation, ancestral reconstruction, evolutionary rate estimation, and simulation. Its modeling repertoire includes phylogenetic stochastic context–free grammars and phylo-hidden Markov models. Following earlier tests of XRATE as a machine-learning tool suitable for alignment annotation, we now report the first tests of XRATE as a precise quantitative instrument for estimating evolutionary rates. We implement a codon model similar to that of Goldman and Yang (1994) (A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11: 725–736) and show that XRATE's parameter estimates are consistent with those of PAML. To demonstrate its utility, we apply the model to measure the difference in selective strength ({omega}) between intracellular and secreted regions of type I transmembrane proteins. In 215 of 303 instances, a complex model with individual {omega} for each region provides a better fit to the data than the simpler single {omega} value model. Secreted portions of type I transmembrane proteins show an elevation in {omega} similar to that seen for secreted protein genes. Less stringent purifying selection is thus a general property of the extracellular milieu, rather than being specific to only soluble and secreted proteins.

Key Words: evolutionary rates • expectation maximization • transmembrane proteins • stochastic context–free grammar


Jeffrey Thorne, Associate Editor


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